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Stephanie A. Hagstrom, Mabel Duyao, Michael A. North, Tiansen Li; Retinal Degeneration in tulp1−/− Mice: Vesicular Accumulation in the Interphotoreceptor Matrix. Invest. Ophthalmol. Vis. Sci. 1999;40(12):2795-2802.
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purpose. The Tulp1 gene is a member of the tubby gene
family with unknown function. Mutations in the human TULP1 gene cause autosomal recessive retinitis
pigmentosa. To understand the pathogenic mechanism associated with TULP1 mutations and to explore the physiologic function
of this protein, we examined tissue distribution of the Tulp1 protein
in normal mice and the photoreceptor disease phenotype in Tulp1–ablated mice.
methods. Tissue distribution of the Tulp1 protein in normal mice was examined by
immunoblotting and immunocytochemistry. The disease phenotype in tulp1 −/− mice was studied by light and
electron microscopy, electroretinography (ERG), and
immunocytochemistry. These results were compared with another mouse
model of retinal degeneration carrying a rhodopsin mutation.
results. Tulp1 is found exclusively in photoreceptors, localizing predominantly
in the inner segments. It is a soluble protein with an apparent
molecular weight of approximately 70 kDa. Photoreceptor degeneration
developed in tulp1 −/− mice, with early
involvement of both rods and cones. At the early stage of degeneration,
rod and cone opsins, but not peripherin/RDS, exhibited prominent
ectopic localization. Electron microscopy revealed massive accumulation
of extracellular vesicles surrounding the distal inner segments.
conclusions. The function of Tulp1 is required to maintain viability of rod and cone
photoreceptors. Extracellular vesicular accumulation is not a common
phenomenon associated with photoreceptor degeneration but appears to be
a distinct ultrastructural feature shared by a small group of retinal
disease models. The defect in tulp1 −/− mice
may be consistent with a loss of polarized transport of nascent opsin
to the outer segments.
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